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• W2013112429 abstract "Although ultraviolet B (UVB) irradiation perturbs the skin barrier, little is known about the mechanism(s) with respect to the metabolism of ceramide (Cer). We examined changes in intercellular lipids in murine stratum corneum following UVB irradiation. A single UVB (75 mJ per cm2) irradiation caused a significant increase in transepidermal water loss, which plateaued at day 4. In parallel, covalently bound Cer was significantly decreased with the greatest decrease at days 3–4. In contrast, the levels of other free, non-bound lipids (including Cer or acylceramides) were significantly increased for Cer, or remained unchanged at day 4 compared with non-irradiated controls. RT-PCR analysis demonstrated a significant decrease in mRNA encoding transglutaminase-1 (TGase1). The peak occurred 2–4 d after a single UVB irradiation, a time when covalently bound Cer was significantly downregulated in concert with the disruption of the skin barrier. Furthermore, UVB-induced epidermal hyperplasia occurred to the greatest extent between 2 and 4 d following UVB irradiation. These results suggest that decreases in covalently bound Cer in the stratum corneum are mediated via the downregulation of TGase-1 as well as by the rapid induction of epidermal hyperplasia, which is attributable to the perturbation of the skin barrier induced by UVB irradiation. Although ultraviolet B (UVB) irradiation perturbs the skin barrier, little is known about the mechanism(s) with respect to the metabolism of ceramide (Cer). We examined changes in intercellular lipids in murine stratum corneum following UVB irradiation. A single UVB (75 mJ per cm2) irradiation caused a significant increase in transepidermal water loss, which plateaued at day 4. In parallel, covalently bound Cer was significantly decreased with the greatest decrease at days 3–4. In contrast, the levels of other free, non-bound lipids (including Cer or acylceramides) were significantly increased for Cer, or remained unchanged at day 4 compared with non-irradiated controls. RT-PCR analysis demonstrated a significant decrease in mRNA encoding transglutaminase-1 (TGase1). The peak occurred 2–4 d after a single UVB irradiation, a time when covalently bound Cer was significantly downregulated in concert with the disruption of the skin barrier. Furthermore, UVB-induced epidermal hyperplasia occurred to the greatest extent between 2 and 4 d following UVB irradiation. These results suggest that decreases in covalently bound Cer in the stratum corneum are mediated via the downregulation of TGase-1 as well as by the rapid induction of epidermal hyperplasia, which is attributable to the perturbation of the skin barrier induced by UVB irradiation. ceramide cornified lipid envelope free fatty acid high-performance thin-layer chromatography sodium dodecyl sulfate transepidermal water loss transglutaminase-1 ultraviolet Exposure of the skin to ultraviolet (UV) radiation induces various harmful effects in that tissue, such as hyperplasia, increases in roughness, wrinkle formation, pigmentation and inflammation (Seidl, 1963Seidl E. On the effectiveness of different UV rays on erythema and pigmentation.Strahlentherapie. 1963; 121: 450-463PubMed Google Scholar;Makki et al., 1979Makki S. Barbenel J.C. Agache P. A quantitative method for the assessment of the microtopography of human skin.Acta Derm Venereol. 1979; 59: 285-291PubMed Google Scholar;Bissett et al., 1987Bissett D.L. Hannon D.P. Orr T.V. An animal model of solar-aged skin: Histological, physical, and visible changes in UV-irradiated hairless mouse skin.Photochem Photobiol. 1987; 46: 367-378Crossref PubMed Scopus (253) Google Scholar;Imokawa et al., 1995Imokawa G. Takema Y. Yorimoto Y. Tsukahara K. Kawai M. Imayama S. Degree of ultraviolet-induced tortuosity of elastic fibers in rat skin is age dependent.J Invest Dermatol. 1995; 105: 254-258https://doi.org/10.1111/1523-1747.ep12317607Crossref PubMed Scopus (52) Google Scholar), and disruption of the epidermal barrier (Abe and Mayuzumi, 1979Abe T. Mayuzumi J. The change and recovery of human skin barrier functions after ultraviolet light irradiation.Chem Pharm Bull (Tokyo). 1979; 27: 458-462Crossref PubMed Scopus (29) Google Scholar;Solomon and Lowe, 1979Solomon A.E. Lowe N.J. Percutaneous absorption in experimental epidermal disease.Br J Dermatol. 1979; 100: 717-722Crossref PubMed Scopus (28) Google Scholar;Lamaud and Schalla, 1984Lamaud E. Schalla W. Influence of irradiation on penetration of hydrocortisone. In vivo study in hairless rat skin.Br J Dermatol. 1984; 111: 152-157Crossref PubMed Scopus (27) Google Scholar;McAuliffe and Blank, 1991McAuliffe D.J. Blank I.H. Effects of UVA (320–400 nm) on the barrier characteristics of the skin.J Invest Dermatol. 1991; 96: 758-762https://doi.org/10.1111/1523-1747.ep12471711Crossref PubMed Scopus (31) Google Scholar). Epidermal ceramides (Cer) and their metabolites play critical roles in maintaining cutaneous barrier homeostasis (Elias and Friend, 1975Elias P.M. Friend D.S. The permeability barrier in mammalian epidermis.J Cell Biol. 1975; 65: 180-191https://doi.org/10.1083/jcb.65.1.180Crossref PubMed Scopus (573) Google Scholar;Gray et al., 1982Gray G.M. White R.J. Williams R.H. Yardley H.J. Lipid composition of the superficial stratum corneum cells of pig epidermis.Br J Dermatol. 1982; 106: 59-63Crossref PubMed Scopus (96) Google Scholar;Elias, 1983Elias P.M. Epidermal lipids, barrier function, and desquamation.J Invest Dermatol. 1983; 80: 44s-49shttps://doi.org/10.1111/1523-1747.ep12537108Abstract Full Text PDF PubMed Google Scholar;Landmann, 1986Landmann L. Epidermal permeability barrier: Transformation of lamellar granule-disks into intercellular sheets by a membrane-fusion process, a freeze-fracture study.J Invest Dermatol. 1986; 87: 202-209https://doi.org/10.1111/1523-1747.ep12695343Abstract Full Text PDF PubMed Scopus (168) Google Scholar) and decreased levels of Cer in the stratum corneum perturb the barrier (Holleran et al., 1991Holleran W.M. Man M.Q. Gao W.N. Menon G.K. Elias P.M. Feingold K.R. Sphingolipids are required for mammalian epidermal barrier function. Inhibition of sphingolipid synthesis delays barrier recovery after acute perturbation.J Clin Invest. 1991; 88: 1338-1345Crossref PubMed Scopus (213) Google Scholar;Imokawa et al., 1991Imokawa G. Abe A. Jin K. Higaki Y. Kawashima M. Hidano A. Decreased level of ceramides in stratum corneum of atopic dermatitis: An etiologic factor in atopic dry skin?.J Invest Dermatol. 1991; 96: 523-526https://doi.org/10.1111/1523-1747.ep12470233Abstract Full Text PDF PubMed Scopus (898) Google Scholar). In this connection, Elias's group reported the upregulation of de novo Cer synthesis in murine epidermis (Holleran et al., 1997Holleran W.M. Uchida Y. Halkier-Sorensen L. Haratake A. Hara M. Epstein J.H. Elias P.M. Structural and biochemical basis for the UVB-induced alterations in epidermal barrier function.Photodermatol Photoimmunol Photomed. 1997; 13: 117-128Crossref PubMed Scopus (113) Google Scholar) and in cultured human keratinocytes (Farrell et al., 1998Farrell A.M. Uchida Y. Nagiec M.M. Harris I.R. Dickson R.C. Elias P.M. Holleran W.M. UVB irradiation up-regulates serine palmitoyltransferase in cultured human keratinocytes.J Lipid Res. 1998; 39: 2031-2038Abstract Full Text Full Text PDF PubMed Google Scholar) following UVB irradiation, suggesting the possibility that the UVB-induced disruption of the skin barrier is not associated with decreased levels of Cer in the stratum corneum. Recently,Meguro et al., 1999Meguro S. Arai Y. Masukawa K. Uie K. Tokimitsu I. Stratum corneum lipid abnormalities in UVB-irradiated skin.Photochem Photobiol. 1999; 69: 317-321https://doi.org/10.1562/0031-8655(1999)069&#60;0317:CAIUIS>2.3.CO;2Crossref PubMed Google Scholar, Meguro et al., 2000Meguro S. Arai Y. Masukawa Y. Uie K. Tokimitsu I. Relationship between covalently bound ceramides and transepidermal water loss (TEWL).Arch Dermatol Res. 2000; 292: 463-468https://doi.org/10.1007/s004030000160Crossref PubMed Scopus (108) Google Scholar demonstrated decreases in covalently bound Cer in the stratum corneum following UVB irradiation with the concomitant disintegration of lipid lamellae. Although it seems likely that covalently bound Cer rather than unbound Cer plays a role in the UVB-induced disruption of the skin barrier, no data on concentration dependence were reported and only a single time point was examined, which was not sufficient to clarify the role of covalently bound Cer in the UVB-induced barrier disruption. Lipids in the stratum corneum comprise a distinctive mixture that is present in the intercellular domain. Most of them are easily removed by extraction with polar organic solvents (Wertz and Downing, 1986Wertz P.W. Downing D.T. Covalent attachment of omega-hydroxyacid derivatives to epidermal macromolecules: A preliminary characterization.Biochem Biophys Res Commun. 1986; 137: 927-992Google Scholar). Following such extraction, however, subsequent alkaline hydrolysis liberates additional lipids, which are bound covalently to the cornified envelope. More than half of those are hydroxyceramides that are thought to be critical for epidermal barrier function as well as corneocyte cohesion (Swartzendruber et al., 1987Swartzendruber D.C. Wertz P.W. Madison K.C. Downing D.T. Evidence that the corneocyte has a chemically bound lipid envelope.J Invest Dermatol. 1987; 88: 709-713https://doi.org/10.1111/1523-1747.ep12470383Abstract Full Text PDF PubMed Scopus (303) Google Scholar;Meguro et al., 1999Meguro S. Arai Y. Masukawa K. Uie K. Tokimitsu I. Stratum corneum lipid abnormalities in UVB-irradiated skin.Photochem Photobiol. 1999; 69: 317-321https://doi.org/10.1562/0031-8655(1999)069&#60;0317:CAIUIS>2.3.CO;2Crossref PubMed Google Scholar;Behne et al., 2000Behne M. Uchida Y. Seki T. de Montellano P.O. Elias P.M. Holleran W.M. Omega-hydroxyceramides are required for corneocyte lipid envelope (CLE) formation and normal epidermal permeability barrier function.J Invest Dermatol. 2000; 114: 185-192Crossref PubMed Scopus (137) Google Scholar). To clarify the relationship between the UVB irradiation-induced disruption of the cutaneous barrier and levels of covalently bound Cer in the stratum corneum, we examined sequential changes in levels of covalently bound Cer within the stratum corneum following UVB irradiation in relation to levels of other intercellular lipids, barrier disruption, and transglutaminase-1 (TGase 1) mRNA expression as well as epidermal hyperplasia. UVB irradiation at a dose of 75 mJ per cm2 perturbed the skin barrier expressed as an increase in transepidermal water loss (TEWL) (Figure 1a). Within 12 h, the TEWL began to increase significantly and reached a plateau around day 4, which was followed by a gradual return to the unirradiated level at day 10. Significant disruption of the barrier was elicited at a dose of 37 mJ per cm2 and increased in a concentration-dependent manner (Figure 1b). It is well known that intercellular lipids play a crucial role in maintaining the barrier function of the skin. Despite the fact that the cutaneous barrier function (as evaluated by TEWL) was significantly perturbed by UVB irradiation at 75 mJ per cm2, intercellular lipids extracted by the Bligh/Dyer method without alkali treatment were not significantly decreased in the stratum corneum at day 4 even though the TEWL had significantly increased and reached a plateau at that time (Figure 2). Although an upregulation of sphingolipid synthesis was reported following UVB irradiation (Holleran et al., 1997Holleran W.M. Uchida Y. Halkier-Sorensen L. Haratake A. Hara M. Epstein J.H. Elias P.M. Structural and biochemical basis for the UVB-induced alterations in epidermal barrier function.Photodermatol Photoimmunol Photomed. 1997; 13: 117-128Crossref PubMed Scopus (113) Google Scholar;Farrell et al., 1998Farrell A.M. Uchida Y. Nagiec M.M. Harris I.R. Dickson R.C. Elias P.M. Holleran W.M. UVB irradiation up-regulates serine palmitoyltransferase in cultured human keratinocytes.J Lipid Res. 1998; 39: 2031-2038Abstract Full Text Full Text PDF PubMed Google Scholar), the UVB-induced disruption of the barrier was accompanied by significant increases in levels of free Cer and free fatty acids (FFA) in the stratum corneum, the former of which occurred in a UVB concentration-dependent manner at day 4 following UVB irradiation (Figure 3). Among those Cer, the levels of acylceramides (Cer(EOS) and Cer(EOH)), Cer(AS), and Cer(AP) were significantly increased (Figure 4 and Table I). These results support the hypothesis that among the UVB-induced alterations of lipids present in the stratum corneum, only the decrease in covalently bound Cer correlates with the increase in TEWL during UVB-induced barrier disruption.Figure 3Unbound ceramide (Cer) levels in the stratum corneum after ultraviolet B (UVB) irradiation. UVB irradiation increased unbound Cer levels in the stratum corneum in a concentration-dependent manner on day 4. Lipid levels were calculated by dried stratum corneum weight. Mean±SD, n=3—8, *p<0.05, ***p<0.001 vs 0 mJ per cm2.View Large Image Figure ViewerDownload (PPT)Figure 4Acylceramide level in the stratum corneum after ultraviolet B (UVB) irradiation. Following UVB irradiation (75 mJ per cm2), unbound ceramide (Cer) levels in the stratum corneum were analyzed at day 4. Lipid levels were calculated by dried stratum corneum weight. Mean±SD, n=5, *p<0.05 vs 0 mJ per cm2. The Cer nomenclatures used in this figure are described in Table I.View Large Image Figure ViewerDownload (PPT)Table ICeramide (Cer) nomenclatures used in this studyAminobond fatty acidSphingoid baseCer(EOS)ω-hydroxy fatty acid ester-linked to linoleic acidSphingosineCer(NS)Non-hydroxy fatty acidSphingosineCer(NP)Non-hydroxy fatty acidPhytosphingosineCer(EOH)ω-hydroxy fatty acid ester-linked to linoleic acid6-hydroxy-4-sphingosineCer(AS)α-hydroxy fatty acidSphingosineCer(AP)α-hydroxy fatty acidPhytosphingosineCer(AH)α-hydroxy fatty acid6-hydroxy-4-sphingosine Open table in a new tab As for free Cer, covalently bound Cer may play a role in barrier homeostasis (Meguro et al., 2000Meguro S. Arai Y. Masukawa Y. Uie K. Tokimitsu I. Relationship between covalently bound ceramides and transepidermal water loss (TEWL).Arch Dermatol Res. 2000; 292: 463-468https://doi.org/10.1007/s004030000160Crossref PubMed Scopus (108) Google Scholar). The level of covalently bound Cer isolated by alkaline treatment after the extraction of free Cer by the Bligh/Dyer method was significantly downregulated in a concentration-dependent manner, almost to 55% of the unirradiated level at day 4 after UVB exposure at a dose of 75 mJ per cm2 (Figure 5). Further, sphingolipids released by alkaline treatment of cornified envelopes at day 4 following a single UVB exposure included only ω-hydroxyceramide, but not ω-hydroxyglucosylceramide (Figure 6). In the UVB-exposed skin (75 mJ per cm2), the level of covalently bound Cer in the stratum corneum was significantly decreased at days 3 and 4 following the single UVB irradiation and gradually returned to the unirradiated level by day 10 (Figure 7), a pattern that was very consistent with the increased TEWL (Figure 1a).Figure 6High-performance thin-layer liquid chromatography (HPTLC) of intercellular lipids extracted from murine stratum corneum on day 4 following UVB irradiation. Sphingolipids released by alkaline treatment from cornified envelopes following a single UVB exposure were analyzed by HPTLC. Only ω-hydroxyceramide, not ω-hydroxyglucosylceramide, covalently bound to Cer in the stratum corneum is decreased after UVB irradiation. The Cer nomenclatures used in this figure are described in Table I. (A) Covalently bound lipids extracted following alkali treatment. (B) Unbound lipids extracted by Bligh/Dyer extraction: (1) Standard, (2) 0 mJ per cm2, (3) 75 mJ per cm2. (a) ω-hydroxyceramide A, (b) ω-hydroxyceramide B, (c) Cer(EOS), (d) Cer(NS), (e) Cer(NP), (f) Cer(EOH), (g) Cer(AS), (h) Cer(AP), (i) Cer(AH).View Large Image Figure ViewerDownload (PPT)Figure 7Covalently bound ceramide (Cer) in the stratum corneum after ultraviolet B (UVB) irradiation. Following a single dose of UVB irradiation (75 mJ per cm2), the levels of covalently bound Cer were decreased to a maximum extent on day 3, which was consistent with the increase in transepidermal water loss. Lipid levels were calculated by dried stratum corneum weight. Mean±SD, n=3–5, *p<0.05, **p<0.01 versus day 0.View Large Image Figure ViewerDownload (PPT) Since TGase 1 is thought to be associated with the attachment of ω-hydroxyceramides to involucrin by ester bond formation (Nemes et al., 1999Nemes Z. Marekov L.N. Fesus L. Steinert P.M. A novel function for transglutaminase 1: Attachment of long-chain omega-hydroxyceramides to involucrin by ester bond formation.Proc Natl Acad Sci USA. 1999; 96: 8402-8407https://doi.org/10.1073/pnas.96.15.8402Crossref PubMed Scopus (222) Google Scholar), we determined the expression of TGase 1 mRNA in UVB-irradiated epidermis. Exposure of murine (BALB/c) skin to UVB at 37 mJ per cm2 induced a significant decrease in the expression of TGase 1 mRNA transcripts at 2–4 d post-irradiation (Figure 8). It is well known that UVB irradiation induces epidermal hyperplasia (Haratake et al., 1997aHaratake A. Uchida Y. Mimura K. Elias P.M. Holleran W.M. Intrinsically aged epidermis displays diminished UVB-induced alterations in barrier function associated with decreased proliferation.J Invest Dermatol. 1997; 108: 319-323https://doi.org/10.1111/1523-1747.ep12286474Crossref PubMed Scopus (69) Google Scholar, Haratake et al., 1997bHaratake A. Uchida Y. Schmuth M. et al.UVB-induced alterations in permeability barrier function: Roles for epidermal hyperproliferation and thymocyte-mediated response.J Invest Dermatol. 1997; 108: 769-775https://doi.org/10.1111/1523-1747.ep12292163Crossref PubMed Scopus (152) Google Scholar). In UVB (75 mJ per cm2)-irradiated skin, the thickness of the epidermis was significantly increased and reached a plateau at day 4 (Figure 9). This increase became quite drastic from day 2 to day 4, a time when the decrease in covalently bound Cer occurred (Figure 7). To clarify the contribution of epidermal hyperplasia to the decreased level of covalently bound Cer in the stratum corneum, we determined if treatments known to induce epidermal hyperplasia (such as tape stripping or SDS washing) affect the levels of covalently bound Cer or non-bound Cer in the stratum corneum. Levels of covalently bound Cer were significantly decreased 2 d after tape stripping or SDS treatment (Figure 10), whereas the levels of non-bound Cer remained unchanged (Figure 11). These results suggest that the decreased level of bound Cer is highly associated with epidermal hyperplasia.Figure 11Ceramide (Cer) levels in hyperproliferating epidermis. Unbound Cer levels did not change in the stratum corneum of hyperproliferating epidermis induced by tape stripping or by sodium dodecyl sulfate (SDS) treatment. SDS, continuous SDS treatment; TS, tape stripping. Mean±SD, n=3.View Large Image Figure ViewerDownload (PPT) In this study, a single UVB irradiation at a dose of 75 mJ per cm2 caused a significant increase in TEWL, an indicator of the barrier function of the skin. This increase occurred in a concentration-dependent manner with a plateau at day 4 and a return to the control level by day 10. In parallel, covalently bound Cer was significantly decreased in a concentration-dependent manner with the maximum effect at days 3–4 and a return to the control level by day 7. The observed decrease in covalently bound Cer at 4 days post-irradiation was not associated with decreases in other unbound, free sphingolipids, but rather with significant increases in unbound, free Cer and FFA. Thus, based upon recent notions that the decreased level of intercellular lipids in the stratum corneum is primarily responsible for the aberrant barrier function of the skin (Grubauer et al., 1989Grubauer G. Feingold K.R. Harris R.M. Elias P.M. Lipid content and lipid type as determinants of the epidermal permeability barrier.J Lipid Res. 1989; 30: 89-96Abstract Full Text PDF PubMed Google Scholar), it seems likely that among changes in a variety of intercellular lipids, only the decrease in covalently bound Cer is paralleled by the increase in TEWL, suggesting a close association between the alteration of covalently bound Cer and the UVB-induced perturbation of the skin barrier. Recently,Macheleidt et al., 2002Macheleidt O. Kaiser H.W. Sandhoff K. Deficiency of epidermal protein-bound omega-hydroxyceramides in atopic dermatitis.J Invest Dermatol. 2002; 119: 166-173https://doi.org/10.1046/j.1523-1747.2002.01833.xCrossref PubMed Scopus (197) Google Scholar reported that decreases in covalently bound Cer and in free Cer occur in atopic dermatitis as a result of downregulation of the de novo synthesis of Cer. But Elias's group demonstrated the upregulation of serine palmitoyltransferase (SPT) mRNA transcripts and activity in cultured human keratinocytes and the de novo synthesis of Cer in mouse epidermis following UVB irradiation (Holleran et al., 1997Holleran W.M. Uchida Y. Halkier-Sorensen L. Haratake A. Hara M. Epstein J.H. Elias P.M. Structural and biochemical basis for the UVB-induced alterations in epidermal barrier function.Photodermatol Photoimmunol Photomed. 1997; 13: 117-128Crossref PubMed Scopus (113) Google Scholar;Farrell et al., 1998Farrell A.M. Uchida Y. Nagiec M.M. Harris I.R. Dickson R.C. Elias P.M. Holleran W.M. UVB irradiation up-regulates serine palmitoyltransferase in cultured human keratinocytes.J Lipid Res. 1998; 39: 2031-2038Abstract Full Text Full Text PDF PubMed Google Scholar). Thus, it seems reasonable to assume that the observed significant decrease in covalently bound Cer induced by UVB irradiation is mediated via biochemical mechanism(s) that are completely distinct from atopic dermatitis, where all Cer species (including covalently bound Cer) are significantly downregulated possibly due to the decreased expression of SPT. As for the potential mechanism(s) that leads to the deficiency in covalently bound Cer in UVB-exposed skin, since UVB radiation affects the gene expression of cytochrome P-450 in keratinocytes (Wei et al., 1999Wei Y.D. Rannug U. Rannug A. UV-induced CYP1A1 gene expression in human cells is mediated by tryptophan.Chem Biol Interact. 1999; 118: 127-140https://doi.org/10.1016/S0009-2797(98)00118-5Crossref PubMed Scopus (82) Google Scholar), ω-hydroxylation via cytochrome P-450 could be inhibited directly or indirectly by UVB; this would result in decreased levels of ω-hydroxyceramides, which would in turn lead to the deficiency in covalently bound Cer. But because levels of ω-hydroxyceramide also contribute to the synthesis of acylceramide (Holleran et al., 1997Holleran W.M. Uchida Y. Halkier-Sorensen L. Haratake A. Hara M. Epstein J.H. Elias P.M. Structural and biochemical basis for the UVB-induced alterations in epidermal barrier function.Photodermatol Photoimmunol Photomed. 1997; 13: 117-128Crossref PubMed Scopus (113) Google Scholar), our results that the concomitant and significant increase in levels of acylceramide occurs in the stratum corneum of UVB-exposed skin seem to argue against the involvement of cytochrome P-450. Recent studies have revealed that ω-hydroxyceramides are ester-linked by the action of TGase 1 to glutamine and to glutamate residues of a number of cell envelope structural proteins, most notably involucrin, which serve as cornified cell envelope proteins bound to Cer and thus contribute to the barrier function of the epidermis (Marekov and Steinert, 1998Marekov L.N. Steinert P.M. Ceramides are bound to structural proteins of the human foreskin epidermal cornified cell envelope.J Biol Chem. 1998; 273: 17763-17770https://doi.org/10.1074/jbc.273.28.17763Crossref PubMed Scopus (182) Google Scholar;Nemes et al., 1999Nemes Z. Marekov L.N. Fesus L. Steinert P.M. A novel function for transglutaminase 1: Attachment of long-chain omega-hydroxyceramides to involucrin by ester bond formation.Proc Natl Acad Sci USA. 1999; 96: 8402-8407https://doi.org/10.1073/pnas.96.15.8402Crossref PubMed Scopus (222) Google Scholar).Kuramoto et al., 2002Kuramoto N. Takizawa T. Takizawa T. Matsuki M. Morioka H. Robinson J.M. Yamanishi K. Development of ichthyosiform skin compensates for defective permeability barrier function in mice lacking transglutaminase 1.J Clin Invest. 2002; 109: 243-250https://doi.org/10.1172/JCI200213563Crossref PubMed Scopus (81) Google Scholar have consistently reported that TGase 1 (-/-) knockout mice have perturbed skin barrier function. It has been demonstrated that TGase 1 mRNA expression is decreased after UVB-irradiation using human skin reconstituted in vitro (Bernerd and Asselineau, 1997Bernerd F. Asselineau D. Successive alteration and recovery of epidermal differentiation and morphogenesis after specific UVB-damages in skin reconstructed in vitro.Dev Biol. 1997; 183: 123-138Crossref PubMed Scopus (140) Google Scholar). In our study, expression of TGase 1 mRNA was significantly downregulated 2–4 d after UVB-irradiation. This suggests that UVB-induced downregulation of TGase 1 may be responsible for the observed decrease in covalently bound Cer, although measurement of TGase 1 activity (which cannot be distinguished from TGase 3 activity using the standard enzymatic assay) will be required for a more precise evaluation. Haratake et al., 1997aHaratake A. Uchida Y. Mimura K. Elias P.M. Holleran W.M. Intrinsically aged epidermis displays diminished UVB-induced alterations in barrier function associated with decreased proliferation.J Invest Dermatol. 1997; 108: 319-323https://doi.org/10.1111/1523-1747.ep12286474Crossref PubMed Scopus (69) Google Scholar, Haratake et al., 1997bHaratake A. Uchida Y. Schmuth M. et al.UVB-induced alterations in permeability barrier function: Roles for epidermal hyperproliferation and thymocyte-mediated response.J Invest Dermatol. 1997; 108: 769-775https://doi.org/10.1111/1523-1747.ep12292163Crossref PubMed Scopus (152) Google Scholar have already reported that hyperproliferation induced by UVB irradiation is associated with barrier disturbance. In our study, a similar marked epidermal hyperplasia was observed especially between days 2 and 4 following UVB irradiation in concert with a decrease in covalently bound Cer. Therefore, we attempted to determine the effects of hyperproliferation elicited by SDS treatment or by tape stripping on the level of covalently bound Cer in the stratum corneum. We found that treatments that induce hyperproliferation significantly diminished the level of covalently bound Cer, despite the lack of effect on non-bound Cer levels, suggesting the possibility that a definite relationship exists between hyperproliferation and decreased levels of covalently bound Cer. The precise mechanism(s) involved in the interrelationships among hyperproliferation, decreased expression of TGase 1, and decreased levels of covalently bound Cer remain to be clarified. As covalently bound Cer is bound to cornified envelope proteins (mainly involucrin), it is possible that UVB irradiation affects involucrin biosynthesis, resulting in the decrease in covalently bound Cer. It has, however, been reported that there is no alteration in levels of involucrin following UVB irradiation (Bernerd and Asselineau, 1997Bernerd F. Asselineau D. Successive alteration and recovery of epidermal differentiation and morphogenesis after specific UVB-damages in skin reconstructed in vitro.Dev Biol. 1997; 183: 123-138Crossref PubMed Scopus (140) Google Scholar).Hirao et al., 2001Hirao T. Denda M. Takahashi M. Identification of immature cornified envelopes in the barrier-impaired epidermis by characterization of their hydrophobicity and antigenicities of the components.Exp Dermatol. 2001; 10: 35-44https://doi.org/10.1034/j.1600-0625.2001.100105.xCrossref PubMed Scopus (80) Google Scholar recently studied the hydrophobicity and immunoreactivity of these components and reported that a decrease in the binding of ω-hydroxyceramides to involucrin (possibly by TGase) is elicited by UVB irradiation. These results strongly suggest that levels of covalently bound Cer could be downregulated independent of involucrin levels. There may be yet another mechanism that leads to the UVB-induced decrease in covalently bound Cer as follows: if ceramidase activity within the stratum corneum is stimulated by UVB irradiation and degrades covalently bound Cer, it is plausible that covalently bound Cer is also decreased in concert with an increase in covalently bound fatty acid. In our preliminary experiment, however, there was no increase in covalently bound fatty acids in the stratum corneum of UVB-exposed skin at 4 d post-irradiation, which seems to rule out a mechanism involving ceramidase. It remains unclear whether the covalent attachment of ω-hydroxyceramide to cornified envelope proteins to form the cornified lipid envelope (CLE) occur with free ω-hydroxyceramide (the acylceramide species) and/or with ω-hydroxyglucosylceramide (Doering et al., 1999aDoering T. Holleran W.M. Potratz A. Vielhaber G. Elias P.M. Suzuki K. Sandhoff K. Sphingolipid activator proteins are required for epidermal permeability barrier formation.J Biol Chem. 1999; 274: 11038-11045https://doi.org/10.1074/jbc.274.1" @default.
• W2013112429 created "2016-06-24" @default.
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• W2013112429 creator A5065920608 @default.
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• W2013112429 date "2004-12-01" @default.
• W2013112429 modified "2023-10-18" @default.
• W2013112429 title "Decreased Levels of Covalently Bound Ceramide Are Associated with Ultraviolet B-Induced Perturbation of the Skin Barrier" @default.
• W2013112429 cites W1550605561 @default.
• W2013112429 cites W1971811687 @default.
• W2013112429 cites W1974481314 @default.
• W2013112429 cites W1974994627 @default.
• W2013112429 cites W1975986537 @default.
• W2013112429 cites W1976938630 @default.
• W2013112429 cites W1978398621 @default.
• W2013112429 cites W1992742394 @default.
• W2013112429 cites W1996306954 @default.
• W2013112429 cites W1997219163 @default.
• W2013112429 cites W1997523952 @default.
• W2013112429 cites W2022126965 @default.
• W2013112429 cites W2022791658 @default.
• W2013112429 cites W2024324559 @default.
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• W2013112429 cites W2049186012 @default.
• W2013112429 cites W2051767864 @default.
• W2013112429 cites W2056676160 @default.
• W2013112429 cites W2059586549 @default.
• W2013112429 cites W2059714246 @default.
• W2013112429 cites W2067017343 @default.
• W2013112429 cites W2072392419 @default.
• W2013112429 cites W2075490511 @default.
• W2013112429 cites W2077680450 @default.
• W2013112429 cites W2087538729 @default.
• W2013112429 cites W2088021954 @default.
• W2013112429 cites W2104955234 @default.
• W2013112429 cites W2112670625 @default.
• W2013112429 cites W2120568510 @default.
• W2013112429 cites W2124050936 @default.
• W2013112429 cites W2137833752 @default.
• W2013112429 cites W2149688394 @default.
• W2013112429 cites W2158612420 @default.
• W2013112429 cites W2169484065 @default.
• W2013112429 cites W2182444717 @default.
• W2013112429 cites W2187326680 @default.
• W2013112429 cites W2340018524 @default.
• W2013112429 cites W4241611988 @default.
• W2013112429 cites W4294216491 @default.
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